Trial Outcomes & Findings for A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies (NCT NCT01325441)

Last Updated: 2023-11-15

Results Overview

Assessment of safety of napabucasin administered in participants with advanced malignancies for whom weekly paclitaxel was an acceptable option by reporting of adverse events and serious adverse events

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

565 participants

Primary outcome timeframe

The time from the date of first treatment, while the patient is taking napabucasin, and for 30 days after stopping therapy, an average of 4 months.

Results posted on

2023-11-15

Participant Flow

565 participants were enrolled between April 2011 and March 2020.

Participants who died, withdrew consent to survival follow up or were lost to follow up were considered to have completed the study.

Participant milestones

Participant milestones
Measure	Napabucasin 200mg BID Plus Paclitaxel Participants received napabucasin 200mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel Participants received napabucasin 240mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel Participants received napabucasin 400mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel Participants received napabucasin 480mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel Participants received napabucasin 500mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.
Overall Study STARTED	2	185	4	317	57
Overall Study COMPLETED	2	185	4	317	57
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Napabucasin 200mg BID Plus Paclitaxel n=2 Participants Participants received napabucasin 200mg BID administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel n=185 Participants Participants received napabucasin 240mg BID administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel n=4 Participants Participants received napabucasin 400mg BID administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel n=317 Participants Participants received napabucasin 480mg BID administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel n=57 Participants Participants received napabucasin 500mg BID administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Total n=565 Participants Total of all reporting groups
Age, Continuous	56.0 years STANDARD_DEVIATION 19.80 • n=5 Participants	61.3 years STANDARD_DEVIATION 10.14 • n=7 Participants	64.8 years STANDARD_DEVIATION 8.06 • n=5 Participants	62.7 years STANDARD_DEVIATION 10.42 • n=4 Participants	60.5 years STANDARD_DEVIATION 10.72 • n=21 Participants	62.0 years STANDARD_DEVIATION 10.38 • n=10 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	115 Participants n=7 Participants	1 Participants n=5 Participants	174 Participants n=4 Participants	24 Participants n=21 Participants	316 Participants n=10 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	70 Participants n=7 Participants	3 Participants n=5 Participants	143 Participants n=4 Participants	33 Participants n=21 Participants	249 Participants n=10 Participants
Race/Ethnicity, Customized Caucasian	2 Participants n=5 Participants	149 Participants n=7 Participants	4 Participants n=5 Participants	259 Participants n=4 Participants	49 Participants n=21 Participants	463 Participants n=10 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	9 Participants n=7 Participants	0 Participants n=5 Participants	11 Participants n=4 Participants	0 Participants n=21 Participants	20 Participants n=10 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	10 Participants n=7 Participants	0 Participants n=5 Participants	21 Participants n=4 Participants	6 Participants n=21 Participants	37 Participants n=10 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	14 Participants n=7 Participants	0 Participants n=5 Participants	18 Participants n=4 Participants	2 Participants n=21 Participants	34 Participants n=10 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	8 Participants n=4 Participants	0 Participants n=21 Participants	11 Participants n=10 Participants

PRIMARY outcome

Timeframe: The time from the date of first treatment, while the patient is taking napabucasin, and for 30 days after stopping therapy, an average of 4 months.

Outcome measures

Outcome measures
Measure	Napabucasin 200mg BID Plus Paclitaxel n=2 Participants Participants received napabucasin 200mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel n=185 Participants Participants received napabucasin 240mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel n=4 Participants Participants received napabucasin 400mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel n=317 Participants Participants received napabucasin 480mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel n=57 Participants Participants received napabucasin 500mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.
Number of Participants With Adverse Events and Serious Adverse Events	2 Participants	183 Participants	4 Participants	317 Participants	57 Participants

PRIMARY outcome

Timeframe: 28 days

Population: The Phase 1b portion of the study consisted of the first 24 patients enrolled in the study. These 24 patients, who received at least one dose of study drug, comprised the DLT Analysis Set.

Determination of the Recommended Phase 2 dose (RP2D) of napabucasin when administered with paclitaxel in patients with advanced malignancies.

Outcome measures

Outcome measures
Measure	Napabucasin 200mg BID Plus Paclitaxel n=24 Participants Participants received napabucasin 200mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel Participants received napabucasin 240mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel Participants received napabucasin 400mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel Participants received napabucasin 480mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel Participants received napabucasin 500mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.
Determination of the Recommended Phase 2 Dose by Assessing Dose-limiting Toxicities (DLTs)	500 mg	—	—	—	—

SECONDARY outcome

Timeframe: Blood samples drawn on days 16 and 17 of the first study cycle

Population: Sponsor's decision to terminate further development of the napabucasin program. Data were not collected.

To determine the maximum concentration of napabucasin and the area under the plasma concentration vs. time curve of napabucasin when administered in combination with weekly paclitaxel

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, for an anticipated average of six months

Population: Data were not collected.

To assess the preliminary anti-tumor activity, specifically the objective response rate (ORR) of napabucasin administered in combination with paclitaxel. The Objective Response Rate (ORR) is the proportion of participants with a complete response or partial response who have measurable disease at baseline imaging.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 60 months

Population: Patients had a baseline scan and at least 1 disease assessment following the initiation of therapy.

Assessment of the objective response rate (ORR) of napabucasin administered in combination with paclitaxel in patients with advanced malignancies. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; The Objective Response Rate (ORR) is the proportion of participants with a complete response or partial response.

Outcome measures

Outcome measures
Measure	Napabucasin 200mg BID Plus Paclitaxel n=2 Participants Participants received napabucasin 200mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel n=81 Participants Participants received napabucasin 240mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel n=1 Participants Participants received napabucasin 400mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel n=98 Participants Participants received napabucasin 480mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel n=29 Participants Participants received napabucasin 500mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.
The Objective Response Rate of Napabucasin Administered in Combination With Paclitaxel in Patients With Advanced Malignancies	0 Participants	23 Participants	0 Participants	9 Participants	6 Participants

SECONDARY outcome

Timeframe: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 60 months.

Population: Patients who received at least 1 cycle of study treatment and had at least 1 disease assessment following the initiation of therapy. Patients missing imaging assessment following the initiation of treatment are not included in the assessment for DCR.

To determine the disease control rate (CDR) of napabucasin administered in combination with paclitaxel in patients with advanced malignancies. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The Disease Control Rate (DCR) is the proportion of patients whose best overall response is CR, PR or SD.

Outcome measures

Outcome measures
Measure	Napabucasin 200mg BID Plus Paclitaxel n=2 Participants Participants received napabucasin 200mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel n=81 Participants Participants received napabucasin 240mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel n=1 Participants Participants received napabucasin 400mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel n=98 Participants Participants received napabucasin 480mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel n=29 Participants Participants received napabucasin 500mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.
Disease Control Rate	100 percentage of participants Interval 15.8 to 100.0	53.1 percentage of participants Interval 41.7 to 64.3	0 percentage of participants	56.1 percentage of participants Interval 45.7 to 66.1	51.7 percentage of participants Interval 32.5 to 70.6

SECONDARY outcome

Timeframe: The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to 60 months

Population: Patients had a baseline scan and at least 1 on study scan or died from any cause.

The effect of napabucasin given in combination with paclitaxel on Progression Free Survival (PFS) of patients with advanced malignancies. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Outcome measures

Outcome measures
Measure	Napabucasin 200mg BID Plus Paclitaxel n=2 Participants Participants received napabucasin 200mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel n=185 Participants Participants received napabucasin 240mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel n=4 Participants Participants received napabucasin 400mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel n=317 Participants Participants received napabucasin 480mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel n=57 Participants Participants received napabucasin 500mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.
Progression Free Survival of Patients With Advanced Malignancies	NA months insufficient number of participants with events	2.23 months Interval 1.87 to 3.52	NA months insufficient number of participants with events	2.07 months Interval 1.87 to 2.53	2.3 months Interval 1.77 to 3.12

SECONDARY outcome

Timeframe: 4 weeks after the patient has been off study treatment, every 3 months up to 18 months, then every 6 months thereafter until death, up to 118 months

The effect of napabucasin given in combination with paclitaxel on Overall Survival (OS) of patients with advanced malignancies

Outcome measures

Outcome measures
Measure	Napabucasin 200mg BID Plus Paclitaxel n=2 Participants Participants received napabucasin 200mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel n=185 Participants Participants received napabucasin 240mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel n=4 Participants Participants received napabucasin 400mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel n=317 Participants Participants received napabucasin 480mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel n=57 Participants Participants received napabucasin 500mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.
Overall Survival of Patients With Advanced Malignancies	NA months insufficient number of participants with events	7.79 months Interval 5.88 to 9.76	NA months insufficient number of participants with events	6.51 months Interval 5.16 to 7.2	7.10 months Interval 3.75 to 9.07

SECONDARY outcome

Timeframe: Day 17 of cycle 1

Population: No on-treatment biopsies were performed therefore no pharmacodynamic testing on tumor tissue was conducted.

To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin

Outcome measures

Outcome data not reported

Adverse Events

Napabucasin 200mg BID Plus Paclitaxel

Serious events: 1 serious events

Other events: 2 other events

Deaths: 2 deaths

Napabucasin 240mg BID Plus Paclitaxel

Serious events: 15 serious events

Other events: 183 other events

Deaths: 150 deaths

Napabucasin 400mg BID Plus Paclitaxel

Serious events: 2 serious events

Other events: 4 other events

Deaths: 4 deaths

Napabucasin 480mg BID Plus Paclitaxel

Serious events: 28 serious events

Other events: 317 other events

Deaths: 292 deaths

Napabucasin 500mg BID Plus Paclitaxel

Serious events: 7 serious events

Other events: 57 other events

Deaths: 54 deaths

Serious adverse events

Serious adverse events
Measure	Napabucasin 200mg BID Plus Paclitaxel n=2 participants at risk Participants received napabucasin 200mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel n=185 participants at risk Participants received napabucasin 240mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel n=4 participants at risk Participants received napabucasin 400mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel n=317 participants at risk Participants received napabucasin 480mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel n=57 participants at risk Participants received napabucasin 500mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.
Gastrointestinal disorders Vomiting	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.6% 5/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Diarrhoea	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.6% 3/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.2% 7/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.6% 5/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Nausea	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.1% 2/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.95% 3/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Colitis	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.1% 2/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.63% 2/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Intestinal perforation	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Diarrhoea haemorrhagic	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Enterocolitis	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Pneumatosis intestinalis	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Infections and infestations Sepsis	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.1% 2/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Fatigue	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Infections and infestations Cholecystitis infective	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Infections and infestations Clostridium difficile infection	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Mucosal inflammation	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Respiratory, thoracic and mediastinal disorders Respiratory alkalosis	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Pyrexia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Asthenia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Dehydration	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.3% 4/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.5% 2/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Radial nerve palsy	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Syncope	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Hypotension	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.1% 2/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Vascular disorders Hypovolaemic shock	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Blood and lymphatic system disorders Anaemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.63% 2/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Blood and lymphatic system disorders Neutropenia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Renal and urinary disorders Acute kidney injury	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.63% 2/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Renal and urinary disorders Prerenal failure	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.

Other adverse events

Other adverse events
Measure	Napabucasin 200mg BID Plus Paclitaxel n=2 participants at risk Participants received napabucasin 200mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 240mg BID Plus Paclitaxel n=185 participants at risk Participants received napabucasin 240mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 400mg BID Plus Paclitaxel n=4 participants at risk Participants received napabucasin 400mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 480mg BID Plus Paclitaxel n=317 participants at risk Participants received napabucasin 480mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.	Napabucasin 500mg BID Plus Paclitaxel n=57 participants at risk Participants received napabucasin 500mg administered orally, twice daily, in combination with a fixed dose of paclitaxel administered IV weekly on day 3, 10 and 17 of each 28 day cycle.
Gastrointestinal disorders Diarrhoea	100.0% 2/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	74.1% 137/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	100.0% 4/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	84.5% 268/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	86.0% 49/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Nausea	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	56.2% 104/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	75.0% 3/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	56.8% 180/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	66.7% 38/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	52.4% 97/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	46.7% 148/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	43.9% 25/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Vomiting	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	36.2% 67/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	43.5% 138/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	47.4% 27/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Abdominal distension	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	11.9% 22/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.2% 26/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Flatulence	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 13/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.4% 17/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Fatigue	100.0% 2/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	57.8% 107/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	75.0% 3/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	59.6% 189/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	63.2% 36/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Asthenia	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.6% 14/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	9.5% 30/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Oedema peripheral	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	16.8% 31/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	19.9% 63/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	21.1% 12/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Decreased appetite	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	45.9% 85/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	42.3% 134/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	43.9% 25/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Dehydration	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	18.9% 35/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	19.9% 63/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	21.1% 12/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hypokaelemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	15.1% 28/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	18.3% 58/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	19.3% 11/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.1% 15/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	15.8% 50/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.8% 5/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Blood and lymphatic system disorders Anaemia	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	25.4% 47/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	38.8% 123/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	35.1% 20/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Blood and lymphatic system disorders Neutropenia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	9.2% 17/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.1% 32/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.8% 5/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.2% 4/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	9.1% 29/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Neuropathy peripheral	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	19.5% 36/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	11.7% 37/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.5% 6/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	13.0% 24/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	11.7% 37/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.8% 5/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Dysgeusia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.9% 11/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.0% 16/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Skin and subcutaneous tissue disorders Alopecia	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	34.6% 64/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	23.0% 73/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	29.8% 17/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Investigations White blood cell count decreased	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 13/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.8% 28/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Investigations Weight decreased	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	11.9% 22/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	16.7% 53/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	19.3% 11/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Investigations Neutrophil count decreased	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.8% 7/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.3% 23/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Renal and urinary disorders Chromaturia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	17.8% 33/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	15.5% 49/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	14.0% 8/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 13/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.7% 18/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.5% 6/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Constipation	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	22.2% 41/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	15.8% 50/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	21.1% 12/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Dysphagia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.6% 3/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.2% 7/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.8% 5/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.9% 6/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Dry mouth	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.4% 10/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.5% 11/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Gastrointestinal disorders Haemorrhoids	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.54% 1/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.95% 3/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Pain	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.2% 6/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	4.4% 14/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.5% 6/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Pyrexia	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	14.1% 26/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	15.1% 48/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.5% 6/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Chills	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.4% 10/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.0% 16/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Disease progression	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.4% 10/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.7% 18/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Mucosal inflammation	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	6.5% 12/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.2% 7/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.6% 14/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.4% 33/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.5% 6/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.6% 16/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.7% 34/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.8% 5/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.4% 10/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	14.2% 45/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.8% 7/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.3% 23/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Headache	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	14.6% 27/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	6.3% 20/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	14.0% 8/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Dizziness	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	14.6% 27/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	11.0% 35/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	12.3% 7/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Encephalopathy	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Nervous system disorders Paraesthesia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.8% 7/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.2% 7/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	100.0% 2/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	28.1% 52/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	23.0% 73/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	22.8% 13/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	23.2% 43/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	13.9% 44/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	19.3% 11/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Musculoskeletal and connective tissue disorders Back pain	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	14.6% 27/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.8% 28/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.5% 6/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	4.3% 8/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	6.9% 22/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.5% 6/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	11.9% 22/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	6.3% 20/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.8% 5/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	9.2% 17/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.9% 25/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.7% 5/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.3% 4/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	4.3% 8/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.8% 9/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Skin and subcutaneous tissue disorders Rash	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	9.7% 18/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.5% 11/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.5% 6/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Infections and infestations Urinary tract infection	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	15.7% 29/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	14.8% 47/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	17.5% 10/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Infections and infestations Candida infection	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.2% 4/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.5% 8/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Infections and infestations Upper respiratory tract infection	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	6.5% 12/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	6.3% 20/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Renal and urinary disorders Proteinuria	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.2% 4/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.8% 28/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Psychiatric disorders Insomnia	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	12.4% 23/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	25.0% 1/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	6.9% 22/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	15.8% 9/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Psychiatric disorders Confusional state	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.2% 4/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	50.0% 2/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.8% 9/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	10.5% 6/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Psychiatric disorders Depression	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.9% 11/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	4.1% 13/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Injury, poisoning and procedural complications Fall	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.2% 6/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.2% 10/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 4/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Vascular disorders Hypotension	0.00% 0/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.0% 13/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	8.2% 26/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	5.3% 3/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
General disorders Influenza like illness	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.6% 3/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.8% 9/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Infections and infestations Pharyngitis	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.1% 2/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Infections and infestations Lung infection	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.32% 1/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.6% 3/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	2.2% 7/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	3.5% 2/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.63% 2/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	1.8% 1/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.
Metabolism and nutrition disorders Hypokalaemia	50.0% 1/2 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	7.6% 14/185 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	0.00% 0/4 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	18.3% 58/317 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.	19.3% 11/57 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, up to 118 months.

Additional Information

Tegan Nguyen

Sumitomo Pharma Oncology

Phone: 6176748745

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60